E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative colitis extending proximally beyond the rectum. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary efficacy objective is to demonstrate that the response to the treatment, measured in term of DAI after 4 weeks of treatment, is not inferior in BDP group compared to the one detected in the prednisone group. The primary safety objective is to demostrate a better safety profile in terms of steroid toxicity and reduction of endogenous cortisol production of BDP treatment compared to prednisone treatment after 4 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
Evaluation of efficacy of the two treatments in terms of improvements of disease related symptoms, general condition and disease severity, measured at week 4 and 8. Evaluation of the overall safety profile of the two treatment regimens after 4 and 8 weeks of treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Pre-inclusion criteria at screening visit : •Male or female >18 or <70 years old; •Women with childbearing potential using efficient contraceptive method •History and documented diagnosis of ulcerative colitis, dated from more than 3 months •Rectal bleeding score ≥1 •Stable dosage of ongoing oral mesalazine therapy (maximum dosage 3.2 g/day) or balsalazide (6.7 g/day), or olsalazine (2 g/day) or sulfasalazine (3 g/die) in the last 14 days •Able to understand and to follow the protocol •Having given written informed consent for study participation Inclusion criteria at randomisation (end of run-in period) •Endoscopic score ≥ 1 in one or more colon segments •DAI score ≥3 and <10 •Confirmation of a rectal bleeding score ≥ 1 •Negative stool examination for infectious disease •Absence of modification of concomitant medications since the screening visit (specially for non authorised treatment) ●Negative pregnancy test for women. |
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E.4 | Principal exclusion criteria |
Exclusion criteria at screening : •Women with childbearing potential and without efficient contraceptive method •Pregnant or breast-feeding women •Severe ulcerative colitis or toxic megacolon •Infectious colitis •Ischemic colitis •Colitis induced by drug or radiotherapy •Crohn’s disease •Major gastro-intestinal surgery other than appendectomy •Evolutive active peptic ulcer or medical history of peptic ulcer complications •Non compensated diabetes mellitus •Non controlled arterial hypertension (SBP ≥160 mm Hg and/or DBP≥ 100 mm Hg) •Hypertyroidism •Medical history of cancer or other concomitant diseases that, according to Investigator’s opinion, could interfere with the evaluation of the test drugs •Poorly controlled pulmonary infections (tubercolosis,active mycotic infections) ●Patients receiving oral or injectable corticosteroids (oral Budesonide included)within 30 days from screening visit, rectal corticosteroid(suppositories,enemas,foams),inhaled corticosteroids ,within 14 days from screening visit ●Change in the oral dose of mesalazine treatment within 14 days from screening visit or at a dosage superior to 3 g/day or balsalazide (6.7 g/day), or olsalazine (2 g/day) or sulfasalazine (3 g/die). ●Patients being treated with H2- receptor antagonists or proton pump inhibitors (PPIs) in the previous 2 weeks •Use of immunomodulators or immunodepressants in the previous 3 months •Patients treated with TNF-alfa antagonists in the previous 6 months •Antibiotic treatment that can not be stopped before randomisation •History of drugs or alcohol abuse •Patients who took part to another clinical study in the previous 3 months Exclusion criteria at randomisation (end of run-in period) •Severe ulcerative colitis (DAI > 10). •Positive ova or parasitic stool examination •Ulcerative colitis with endoscopic score < 1 or rectal bleeding score <1 •Ulcerative colitis limited to the rectum •Crohn’disease •Significant hepatic impairment (ALT or AST twice the upper limit of normal range) •Significant renal impaiment (serum creatinine >1.5 mg/dL) •Any abnormal laboratory test which could interfere with the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable will be the percentage of patients with clinical response, defined as a DAI score < 3 or reduced of at least 3 points for patients with a baseline DAI ≥ 7 after 4 weeks of treatment with test drugs. The secondary variables will be: percentage of patients with clinical response after 4 weeks of treatment without steroid-related AEs, including cortisol levels < 5mcg/dL (or <150 nmol/L); percentage of patients with a DAI score ≤ 1 after 4 weeks of treatment; change in DAI total score after 4 weeks of treatment; change in endoscopic score after 4 weeks of treatment; change in CAI total score after 4 and 8 weeks of treatment; change of bleeding score after 4 and 8 weeks of treatment; changes of CPR, ESR, after 4 and 8 weeks of treatment. The primary safety variable will be the percentage of patients with adverse events related to steroidal treatment including serum morning cortisol < 5 mcg/dL ( or <150 nmol/L) during the first 4 weeks of treatment (from Visit 2 to Visit 4). The secondary variables will be: percentage of patients with adverse events related to steroid treatment including morning serum cortisol < 5 mcg (or <150 nmol/L) during the second 4 weeks of treatment (after Visit 4 to Visit 6); changes from baseline to visits after 4 and 8 weeks of treatment in morning cortisol level; changes from baseline to visits after 4 and 8 weeks of treatment in laboratory test parameters; change from baseline to visit 4 and 6 in vital signs; percentage of patients with adverse events related to steroid treatment including morning serum cortisol < 5 mcg (or <150 nmol/L) during the whole treatment period. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of last patient undergoing trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |